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Elimination of Incretin Hormones in Patients With Severe Kidney Failure

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ClinicalTrials.gov Identifier: NCT01391884
Recruitment Status : Completed
First Posted : July 12, 2011
Last Update Posted : September 19, 2012
Sponsor:
Information provided by (Responsible Party):
Bo Feldt-Rasmussen, Rigshospitalet, Denmark

Brief Summary:

The prevalence of type 2 diabetes (T2D) is increasing rapidly worldwide. T2D is characterized by a severely impaired incretin effect. The incretin effect refers to the insulinotropic action of the nutrient-released incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). The incretin effect is defined as the difference in insulin secretory responses between oral and isoglycaemic intravenous glucose challenges (OGTT and IIGI, respectively) and in healthy individuals it accounts for as much as 70% of the insulin response following oral glucose, whereas patients with T2D exhibit an incretin effect in the range of 0 to 30%. Patients with T2D and non-diabetic patients with severe kidney failure share several pathophysiological characteristics, including decreased insulin sensitivity, fasting hyperinsulinaemia and impaired beta-cell function. The reason for these findings remains to be fully elucidated. An ongoing study in our research group is investigating the incretin effect and the incretin hormone secretory responses following OGTT, IIGI and meal ingestion, respectively. In continuation of this study, essential knowledge of metabolism of incretin hormones in an uremic milieu will be obtained in the present study prior to evaluation of the use of incretin-based agents in patients with impaired kidney function. In this second study we evaluate the elimination and biodegradation of GLP-1 and GIP. The biological active incretin hormones are rapidly degraded by the ubiquitous enzyme dipeptidyl peptidase-4 (DPP-4), generating inactive metabolites. The active hormones are however also eliminated by renal clearance, although the importance of this remains questionable. It is likely that the degradation and elimination of the active hormones will be significantly affected in patients with severe kidney impairment.

We hypothesize that elimination and biodegradation of the two incretin hormones, both in it´s active and inactive forms, will be affected in non-diabetic patients with severe kidney failure.


Condition or disease
Uremia

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Study Type : Observational
Actual Enrollment : 24 participants
Observational Model: Case-Control
Time Perspective: Cross-Sectional
Official Title: Elimination and Biodegradation of the Incretin Hormones GLP-1 and GIP in Patients With End-stage Renal Disease
Study Start Date : June 2011
Actual Primary Completion Date : June 2012
Actual Study Completion Date : June 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hormones

Group/Cohort
Dialysis, Non-diabetic
Hemodialysis
Healthy control



Primary Outcome Measures :
  1. Intact GLP-1 concentration [ Time Frame: -60 min - 180 min ]
    During GLP-1 infusion 0-60 min

  2. Total GLP-1 concentration [ Time Frame: -60 min - 180 min ]
    GLP-1 infusion 0-60 min

  3. Intact GIP concentration [ Time Frame: - 60 min - 180 min ]
    GIP infusion 0-60 min

  4. Total GIP infusion [ Time Frame: -60 min - 180 min ]
    GIP infusion 0-60 min



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Ages Eligible for Study:   18 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
  1. Hemodialysis patients
  2. Healthy control subjects
Criteria

1)

Inclusion Criteria:

  • Male or female; aged 18-90 years
  • CKD stage 5 in chronic maintenance dialysis treatment
  • BMI: 18,5-28 kg/m2
  • Normal fasting plasma glucose (<6,1 mM)
  • Normal or impaired glucose tolerance (PG120 min <11,1 mM following OGTT)

Inclusion Criteria:

  • Male or female; aged 18-90 years
  • Healthy including normal kidney function
  • BMI: 18,5-28 kg/m2
  • Normal fasting plasma glucose (<6,1 mM)
  • Normal or impaired glucose tolerance (PG120 min <11,1 mM following OGTT)

1+2)

Exclusion Criteria:

  • Diabetes mellitus
  • Chronic pancreatitis / previous acute pancreatitis
  • Treatment with oral glucocorticoids, calcineurin inhibitors, thiazides, dipeptidyl peptidase 4 (DPP4) inhibitors or other drugs, which could interfere with glucose or lipid metabolism
  • Inflammatory bowel disease
  • Malignant disease
  • Bowel resection
  • Severe anemia (hemoglobin <6.5 mmol/L)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01391884


Locations
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Denmark
Department of Nephrology P, Copenhagen University Hospital, Rigshospitalet
Copenhagen, Denmark, 2100
Sponsors and Collaborators
Bo Feldt-Rasmussen
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Bo Feldt-Rasmussen, MD DMSc, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier: NCT01391884    
Other Study ID Numbers: H-2-2009-158-UREMINC
First Posted: July 12, 2011    Key Record Dates
Last Update Posted: September 19, 2012
Last Verified: September 2012
Keywords provided by Bo Feldt-Rasmussen, Rigshospitalet, Denmark:
Incretin hormones
GLP-1
GIP
Uremia
Dialysis
Additional relevant MeSH terms:
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Uremia
Kidney Diseases
Urologic Diseases